The Wise App Trial for Improving Health Outcomes in PLWH Human Immunodeficiency virus (HIV) continues to affect 1.2 million Americans. Achieving viral suppression through adherence to antiretroviral (ART) therapy is a critical determinant of successful transmission prevention and long-term outcomes in HIV-infected patients. However only about 25% of persons living with HIV (PLWH) in the US are virally suppressed, demonstrating the need for effective interventions that enhance ART adherence. mHealth is a tool that has proven useful in supporting behavior change, but most mHealth tools for PLWH have not been well-developed or evaluated. Given the dearth of useful and likeable apps, the need for improving medication adherence in PLWH, and the great promise of mHealth, we propose to build and test a user-centered smartphone app linked to a smart pill box targeting ART adherence in PLWH. Self- report of medication adherence is often criticized since it typically overestimated adherence especially in unmasked trials. Current adherence assessments, such as patient recall, pill counts and pharmacy refill data, typically detect missed doses long after they occur. Our study will use real-time, wireless monitoring strategies via the Wisepill dispenser, for measuring ART adherence. This will overcome this often cited limitation and provide novel opportunities to proactively prevent virologic rebound and treatment failure. Guided by Fogg's Functional Triad for persuasive technology and building on our earlier user-centered design work, the proposed intervention has the potential to not only improve ART adherence in PLWH, but also have a sustainable public health impact. The aims of our study are to: (1) Build a functional app for HIV self- management linked to a smart pill box (Wise App) for PLWH and assess its usability; (2) Evaluate the impact of the Wise App on medication adherence in underserved PLWH; and (3) Assess PLWH perceptions of the predisposing, enabling, and reinforcing factors for Wise App use through theoretically-guided focus group sessions. The proposed study extends our preliminary work that employed user-centered design methods to identify the content, features, functionalities, and interface of a mobile app to improve health outcomes in PLWH. The user-centered design app we will build will then be linked to a smart pill box so that PLWH can receive feedback on their adherence behaviors. Our study intervention, the Wise App, is relevant, timely, of public health import, and supported by substantial preliminary work. The proposed trial is significant in representing a principled and systematic effort to build, and test the efficacy of a smartphone intervention for ART adherence in PLWH in the US. Importantly, this work has broader implications and will improve our understanding of how to support patients' medication adherence, regardless of treatment target.